Predictive Value of Ercc1 and Xpd Polymorphisms for Clinical Outcomes of Patients Receiving Neoadjuvant Therapy

Excision repair cross complementing 1 (ERCC1) and xeroderma pigmentosum group D (XPD) play important roles in the nucleotide excision repair (NER) pathway. The correlation between ERCC1 polymorphisms (rs11615 and rs3212986) and XPD polymorphisms (rs13181 and rs1799793) with the response rate and overall survival of cancer patients who accept neoadjuvant therapy has been extensively investigated. However, the results are inconclusive. In this study, we performed a meta-analysis to determine the strength of this correlation. A comprehensive literature search was conducted in Medline, PubMed, and Embase up to February 2015. A review of all titles and abstracts was performed by 2 of the authors to screen the articles based on the eligibility criteria. Clinical trials, observational studies, and epidemiological studies describing ERCC polymorphisms and neoadjuvant treatment were considered for review. The response rate was analyzed using pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall survival was assessed using the hazard ratio (HR) with corresponding 95% confidence intervals. In the present meta-analysis, we demonstrated that the ERCC1 rs3212986 polymorphism was significantly correlated with the response rate of esophageal cancer patients to neoadjuvant therapy (OR =  .49, 95% CI = 0.31-0.76, heterogeneity P = 0.480). Furthermore, a considerable correlation was observed between ERCC1 rs11615 and the response rate of esophageal cancer patients to neoadjuvant therapy (OR = 0.228, 95% CI = 0.125-0.418, heterogeneity P = 0.291). No correlation was observed in the meta-analysis of overall survival. The individual studies included in our study differed in their patient selection and therapeutic protocols, which might lead to some bias in the results. These findings indicate that the ERCC1 rs11615 and ERCC1 rs312986 polymorphisms may be candidate pharmacogenomic factors capable of predicting the response rate of esophageal cancer patients who accept neoadjuvant therapy. Further studies are warranted.